Journal Club

Alcohol, Other Drugs, and Health: Current Evidence

March–April 2014

Featured Article

Gabapentin Can Decrease Heavy Drinking and Increase Abstinence for Patients with Alcohol

Dependence

Mason BJ, et al. JAMA Intern Med. 2014;174(1):70–77.

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Study Objective

• To determine whether gabapentin can increase rates of sustained abstinence and decrease rates of heavy drinking.

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Study Design

• A 12-week, double-blind, placebo-controlled randomized dose-ranging trial comparing three groups (N = 150 adults with current alcohol dependence). All groups received counseling.

• The three groups received:

– Gabapentin 900 mg/day

– Gabapentin 1800 mg/day

– Gabapentin 0 mg/day (control)

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Assessing Validity of an Article about Therapy

• Are the results valid?

• What are the results?

• How can I apply the results to patient care?

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Are the Results Valid?

• Were patients randomized?

• Was randomization concealed?

• Were patients analyzed in the groups to which they were randomized?

• Were patients in the treatment and control groups similar with respect to known prognostic variables?

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Are the Results Valid? (cont‘d)

• Were patients aware of group allocation?

• Were clinicians aware of group allocation?

• Were outcome assessors aware of group allocation?

• Was follow-up complete?

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Were patients randomized?

• Yes.– Patients were randomized using a computer-

generated randomization code.– Patients were randomized in a 1:1:1 ratio.

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Was randomization concealed?

• Yes.– The randomization code was kept

by the study pharmacist who administered the medication.

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Were patients analyzed in the groups to which they were

randomized?

• Yes.

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Were the patients in the treatment

and control groups similar?

• Yes.

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Were patients aware of group allocation?

• No.– Patients were blinded to group

allocation.

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Were clinicians aware of group allocation?

• No.– Only the study pharmacist was aware of

group allocation. Other researchers or clinicians were not.

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Were outcome assessors aware of group allocation?

• No.

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Was follow-up complete?

• No.

– The trial was 12 weeks long and patients were administered medication weekly.

– Number of patients who provided 12-week data for analysis: • Gabapentin 900 mg group: 27 of 54

initially enrolled• Gabapentin 1800 mg group: 28 of 47

initially enrolled• Control group: 30 of 49 initially enrolled

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What Are the Results?

• How large was the treatment effect?

• How precise was the estimate of the treatment effect?

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How large was the treatment effect?

• Gabapentin had a significant linear dose effect in increasing rates of abstinence (P = 0.04).

• The rate of 12-week abstinence was:– Gabapentin 900 mg group: 11.1% (95% CI, 5.2%–

22.2%)– Gabapentin 1800 mg group: 17% (95% CI, 8.9%–

30.1%; NNT = 8; OR = 4.8)

– Control: 4.1% (95% CI, 1.1%–13.7%)

• The rate of no heavy drinking at 12 weeks was:– Gabapentin 900 mg group: 29.6% (95% CI, 19.1%–

42.8%)– Gabapentin 1800 mg group: 44.7% (95% CI, 31.4%–

58.8%; NNT = 5; OR = 2.8)– Control: 22.5% (95% CI, 13.6%–37.2%)

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How Can I Apply the Results to Patient Care?

• Were the study patients similar to the patients in my practice?

• Were all clinically important outcomes considered?

• Are the likely treatment benefits worth the potential harm and costs?

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Were the study patients similar to those in my practice?

• The patients were treatment-seeking adult volunteers.

• All were people with current DSM-IV alcohol dependence; the majority had moderate dependence.

• They were excluded if urine toxicology screens revealed the use of any other substances besides alcohol or nicotine.

• They could not have significant medical or psychiatric disorders.

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Were all clinically important outcomes considered?

• Yes.

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Are the likely treatment benefits worth the potential harm and

costs?• Possibly.

– There were no differences in the rate of termination due to adverse events by study arm. Costs were not considered.

– Due to the loss to follow-up, further studies into acceptability and efficacy of gabapentin for treating alcohol use disorders are needed.

– Results may not be generalizable since it was a single-site study.

– The overlapping confidence intervals across the study groups suggest that widespread use of the treatment for dependence should await a larger effectiveness trial.